PROJECT SUMMARY Animals navigate based on self-motion cues and external references, which serve to correct errors accumulated in path integration. Cells in the medial entorhinal cortex (MEC) encode direction, speed and position, and their output could represent the neural basis for path integration. The vestibular system provides information for angular and linear motion, and lesion studies have suggested that it may be important for path integration-based navigation. Whether and how this is done represents a mystery. In recent years, virtual- reality (VR) has become fashionable in exploring the navigation circuit. Remarkably, two-dimensional (2D) grid properties are compromised in head-fixed rodents experiencing VR. The hypothesis to be tested here is that this occurs because inertial (vestibular) signals are in conflict with locomotion and visual cues ? which contrasts with real-world navigation where congruent multisensory cues from vestibular, visual and other modalities all converge to give rise to the sense of motion through space. In VR, only the visual and proprioceptive cues are present, while vestibular cues signal no motion. To test the hypothesis that inertial motion cues are necessary for space coding in the MEC, we have built a one-of-a-kind VR apparatus (mouse is head-fixed and locomoting on an air cushioned Styrofoam ball) that is mounted on top of a motion platform, which can provide inertial accelerations. The visual stimulus creating the VR environment as well as the movement of the platform are both controlled by the locomotion of the mouse and the resulting ball rotation. We will monitor grid cell activity during navigation, while rotation and/or translation multisensory cues are independently and systematically manipulated. Our findings could revolutionize our understanding of the nature and properties of the spatial code in MEC by bridging together diverse expertise and two segregated (navigation/MEC/hippocampus and vestibular/multisensory) communities.